Comparison of the Effect of Keeping Rats in the Mountains and on the Plain on the Development of Streptozotocin-Induced Diabetes and Gastric Ulceration

Abstract

Hypoxia can correct the development of diabetes and its complications in animals and humans, and diabetes exacerbates the gastric ulceration. However, the effect of hypoxia on the gastric ulceration in diabetes remains unknown. The task of the work was to compare the effect of keeping rats in the mountains under moderate natural hypoxia and on the plains on the development of type 1 diabetes and the gastric ulceration. Two weeks after the rats acclimatized to hypoxia (Elbrus region, 2125 m above sea level), they were injected with streptozotocin (STR, 50 or 70 mg/kg) or its vehicle. Simultaneously, rats on the plains were injected with STR (or its vehicle) at the same doses. Indomethacin (IM, 35 mg/kg) was administered two weeks after STR or its vehicle injection in rats after 24 h of fasting, both in the mountains and on the plains, which led to the gastric erosion formation 4 h later. The injection of STR (50 and 70 mg/kg) caused a dose-dependent increase in blood glucose levels in rats both in the mountains and on the plains, which indicates the development of diabetes of varying severity. In rats on the plains the administration of STR (50 and 70 mg/kg) led to a dose-dependent increase in the area of erosions induced by IM compared with those in control animals (STR vehicle). In rats in the mountains, an aggravation of gastric mucosal injury caused by IM was observed, both in control rats (STR vehicle) and in animals with STR-induced diabetes, compared with the gastric injury in rats of the corresponding groups on the plains. The greatest increase in the proulcerogenic effect of STR in the mountains was observed when it was administered at a dose of 70 mg/kg. Thus, persistent moderate hypoxia may lead to an increase in IM-induced gastric ulceration in rats with type 1 diabetes, and, in addition, by itself exacerbate the ulcerogenic effect of IM.